α-(ω-cyanoalkanoyl)-γ-butyrolactone and method for producing the same

ABSTRACT

Disclosed are α-(ω-Cyanoalkanoyl)-γ-butyrolactone represented by the formula: ##STR1## wherein n represents an integer of 7 to 11, and a method for producing the same, which comprises reacting ω-cyano fatty acid ester represented by the formula: 
     
         NC--(CH.sub.2).sub.n --COOR                                (II) 
    
     wherein R represents an alkyl group having 1 to 4 carbon atoms and n has the same meaning as in the above, with γ-butyrolactone in the presence of alkali metal alcoholate represented by the formula: 
     
         R&#39;OM                                                       (III) 
    
     wherein R&#39; represents an alkyl group having 1 to 4 carbon atoms and M represents an alkali metal.

This is a division of application Ser. No. 07/529,897 filed May 29, 1990now U.S. Pat. No. 5,023,351.

BACKGROUND OF THE INVENTION

This invention relates to α-(ω-cyanoalkanoyl)-γ-butyrolactone, which isa novel intermediate lactone in the preparation of ω-hydroxy fatty acid,which is useful as a starting material and intermediate of varioussyntheses, particularly an important intermediate of macrocyclic lactonetype perfumes in the field of perfume industry.

α-(ω-cyanoalkanoyl)-γ-butyrolactone which produced according to thepresent invention is a novel compound.

There have been known many methods for producing ω-hydroxy fatty acidwhich is an important intermediate of macrocyclic lactone type perfumes.Typical examples thereof are introduced in "Perfume ChemicalComprehensive 2", by Osamu Okuda, Hirokawa Shoten, p. 1211 and "PerfumeChemical Comprehensive 3", by Osamu Okuda, Hirokawa Shoten, p.p. 172-174and 176-177.

The above methods include several drawbacks that these have many stepsand are troublesome in handling, expensive agents or agents accompaniedby dangers in handling are often required, and also the yield is poor.

Accordingly, these methods are not advantageous methods in industrialview.

SUMMARY OF THE INVENTION

An object of the present invention is to provideα-(Ω-cyanoalkanoyl)-γ-butyrolactone, a novel compound as a startingmaterial in the preparation of ω-hydroxy fatty acid, which can solve theabove drawbacks in the prior art and a method for producing the same.

The present inventors found that α-(ω-cyanoalkanoyl)-γ-butyrolactonerepresented by the formula: ##STR2## wherein n represents an integer of7 to 11, can be obtained easily at high yield by reacting ω-cyano fattyacid ester represented by the formula:

    NC--(CH.sub.2).sub.n --COOR                                (II)

wherein R represents an alkyl group having 1 to 4 carbon atoms and n hasthe same meaning as in the above, with γ-butyrolactone in the presenceof alkali metal alcoholate represented by the formula:

    R'OM                                                       (III)

wherein R' represents an alkyl group having 1 to 4 carbon atoms and Mrepresents an alkali metal, and accomplished the present invention.

DESCRIPTION OF THE PREFERRED EMBODIMENTS

α-(ω-cyanoalkanoyl)-γ-butyrolactone of the formula (I) obtained by thepresent invention can be easily derived at high yield to ω-hydroxy fattyacid (V) which is an important intermediate of macrocyclic lactone typeperfumes through the steps shown below. ##STR3##

More specifically, α-ω-cyanoalkanoyl)-γ-butyrolactone of the formula (I)can be converted to ω-hydroxy-(ω-3)-keto fatty acid of the formula (IV)by heating in an aqueous solution of alkali metal hydroxide or awater-soluble organic solvent/water mixture to hydrolyze the --CN groupto --COOH group and hydrolyze and decarboxylate the lactone site to a--(CH₂)₃ --OH group.

Then, the --CO-- group of the formula (IV) is reduced to a --CH₂ --group by ordinary procedures, Clemmensen reduction or Wolff-Kishnerreduction to derive the compound (IV) to ω-hydroxy fatty acid (V).

Specific examples of α-(ω-cyanoalkanoyl)-γ-butyrolactone of the formula(I) may include, α-(8-cyanooctanoyl)-γ-butyrolactone,α-(9-cyanononanoyl)-γ-butyrolactone,α-(10-cyanodecanoyl)-γ-butyrolactone,α-(11-cyanoundecanoyl)-γ-butyrolactone andα-(12-dodecanoyl)-γ-butyrolactone.

Specific examples of ω-cyano fatty acid ester of the formula (II) mayinclude methyl 8-cyanooctanate, ethyl 8-cyanooctanate, propyl8-cyanooctanate, butyl 8-cyanooctanate, methyl 9-cyanononanate, ethyl9-cyanononanate, propyl 9-cyanononanate, butyl 9-cyanononanate, methyl10-cyanodecanate, ethyl 10-cyanodecanate, propyl 10-cyanodecanate, butyl10-cyanodecanate, methyl 11-cyanoundecanate, ethyl 11-cyanoundecanate,propyl 11-cyanoundecanate, butyl 11-cyanoundecanate, methyl12-cyandodecanate, ethyl 12-cyanododecanate, propyl 12-cyanododecanate,butyl 12-cyanododecanate and the like.

The ω-cyano fatty acid ester of the formula (II) may be used in therange of 0.3 to 10 mole, preferably 0.5 to 5 mole per mole ofγ-butyrolactone. In the instance where the employed amount is less thanthe lower limit, the yield will be lowered, while in the instance wherethe employed amount exceeds the upper limit, although no problem occursin the yield, the recovery amount of unreacted ω-cyano fatty acid esterof the formula (II) will be increased to make the method disadvantageousin economical view. Both instances are thus not preferable.

Specific examples of alkali metal alcoholate of the formula (III) mayinclude sodium methylate, sodium ethylate, sodium propylate, sodiumbutylate, potassium methylate, potassium ethylate, potassium propylate,potassium butylate and the like. The alkali metal alcoholate shouldadvantageously be used under the state of an alcohol solutioncorresponding to the alcoholate in a viewpoint of operability.

The alkali metal alcoholate of the formula (III) may be used in therange of 0.5 to 2 mole, preferably 0.7 to 1.5 mole per mole ofγ-butyrolactone. In the instance where the employed amount is less thanthe lower limit, the reaction does not proceed sufficiently, while inthe instance where the employed amount exceeds the upper limit, sidereactions will often occur. Both instances are thus not preferable.

In the method of the present invention, a reaction solvent may be usedwith no problem. As the reaction solvent, n-hexane, n-heptane, benzene,toluene, xylene, dioxane, dimethoxyethane, diethoxyethane, diglaim, etc.may be included. When such solvents are used, it is preferable to use asolvent having a boiling point higher than that of the alcohol producedin the reaction.

The reaction temperature is in the range of 50° to 150 ° C., preferably80° to 120 ° C.

The reaction can be carried out under the condition of atmosphericpressure, but may be carried out under the reduced pressure to rapidlyevaporate the alcohol which is used for accelerating the reaction, tothe outside of system.

The reaction time, which is appropriately selected depending on thereaction temperature, kind of starting material charged and the like,may generally be around 1 to 5 hours.

The reaction may be carried out by either a batch system or a continuoussystem.

Isolation and purification of the reaction product can be effectedaccording to a unit operation which is itself well known such asneutralization, extraction, concentration, recrystallization or thelike.

By utilizing α-(ω-cyanoalkanoyl)-γ-butyrolactone of the formula (I)novelly found by the present inventors, ω-hydroxy fatty acid of theformula (V), which is an important intermediate of macrocyclic lactonetype perfumes, can be obtained at high yield by simple operation frominexpensive and easy-available starting material through three stepssignificantly shortened as compared with the conventional methods.Furthermore, α-(ω-cyanoalkanoyl)-γ-butyrolactone of the formula (I) isalso widely useful as an intermediate lactone.

The present invention is described in more detail by referring toexamples.

EXAMPLE 1

18.03 g (80.0 millimole) of methyl 11-cyanoundecanate, 3.44 g (40.0millimole) of γ-butyrolactone and 7.72 g (40.0 millimole) of 28 wt.% ofsodium methylate - methanol solution were charged into a frask andheated and stirred until the internal temperature became 105° to 110 °C. while evaporating off the methanol out of the system over 2 hours.After the completion of the reaction, the system was cooled and madeacidic by use of 43 ml of 1N-HCl, followed by extraction once from 100ml of methylene chloride and two times from 20 ml of methylene chloride.After the methylene chloride solution was dried over magnesium sulfate,concentration was conducted to dryness to obtain pail brown oilyproduct. The obtained oily product was purified with use of a silicagelcolumn by using n-hexane/ethyl acetate (1:1, volume ratio) as adeveloper to obtain 7.93 g (28.4 millimole, yield: 71%) of a whitesolid.

The results of analysis of the white solid are shown below.

(1) m.p. 57° to 59 ° C.

(2) elemental analysis (in terms of C₁₆ H₂₅ NO₃).

    ______________________________________                                                  C          H      N                                                 ______________________________________                                        Calculated (%)                                                                            68.79        9.02   5.01                                          Found (%)   68.67        9.06   5.22                                          ______________________________________                                    

(3) IR (KBr,cm⁻¹), 2920, 2850, 2250, 1780, 1705.

(4) MS (m/e, CI), 280 (M⁺ +1).

(5) 1H-NMR (CDCl₃, δ(ppm)). 1.20˜1.37 (10H, broad), 1.37˜1.50 (2H, m),1.62˜1.69 (4H, m), 2.26˜2.36 (3H, m), 2.56˜2.64 (1H, m), 2.72˜2.80 (1H,m), 2.91˜3.00 (1H, m), 3.68˜3.72 (1H, m), 4.29˜4.41 (2H, m).

From the above respective analysis results, it was confirmed that theproduct was α-(11-cyanoundecanoly)-γ-butyrolactone

EXAMPLES 2 TO 5

With respect to 3.44 g (40.0 millimole) of γ-butyrolactone and 7.72 g(40.0 millimole) of 28 wt.% sodium methylate - methanol solution, theamounts shown in Table 1 of methyl 11-cyanoundecanate were charged ineach example, and heated under stirring. When the evaporation ofmethanol from the reaction system started, the degree of reducedpressure of the reaction system was controlled to 610 to 630 Torr andthen evaporation of methanol was continued until the internaltemperature became 105° to 110 ° C. for 2 hours. After the completion ofthe reaction, the system was cooled and made acidic by use of 43 ml of1N-HCl, followed by extraction once from 100 ml of methylene chlorideand two times from 20 ml of methylene chloride. The product in themethylene chloride solution, α-(11-cyanoundecanoly)-γ-butyrolactone andthe unreacted methyl 11-cyanoundecanate were quantified with use of agas chromatography according to the internal standard method. Theresults are shown in Table 1.

                                      TABLE 1                                     __________________________________________________________________________                        α-(11-cyanoundecanoly)-                                    Charged amount of methyl                                                                   γ-butyrolactone                                                                      Amount of unreacted                                 11-cyanoundecanate                                                                          Produced amount                                                                       Yield                                                                             methyl 11-cyanoundecanate                    Example No.                                                                          g (millimole)                                                                              g (millimole)                                                                          (%) *1)                                                                           g (millimole)                                __________________________________________________________________________    2       6.02 (26.7) 5.50 (19.7)                                                                            83  0.65  (2.9)                                  3       9.01 (40.0) 8.16 (29.2)                                                                            73  2.19  (9.7)                                  4      18.03 (80.0) 9.39 (33.6)                                                                            84  9.91 (44.0)                                  5      36.05 (160)  9.28 (33.2)                                                                            83  27.7  (121)                                  __________________________________________________________________________     Note:                                                                         *1) The yield in Example 2 is the value based on methyl 11cyanoundecanate     having been reacted as a standard. In Examples 3 to 5, the yield is the       value based on butyrolactone charged as a standard.                      

EXAMPLES 6

9.01 g (40.0 millimole) of methyl 11-cyanoundecanate, 3.44 g (40.0millimole) of γ-butyrolactone, 7.72 g (40.0 millimole) of 28 wt.% ofsodium methylate - methanol solution and 10 ml of dioxane were chargedand heated and stirred until the internal temperature became 105° to 107° C. while evaporating the methanol and dioxane to the outside of thesystem over 2 hours. After completion of the reaction, the system wascooled and made acidic by use of 43 ml of 1N-HCl, followed by extractiononce from 100 ml of methylene chloride and two times from 20 ml ofmethylene chloride. The product in the methylene chloride solution,α-(11-cyanoundecanoly)-γ-butyrolactone and the unreacted methyl11-cyanoundecanate were quantified in the same manner as in Example 3.

As a result of the analysis, the producedα-(11-cyanoundecanoly)-γ-butyrolactone was 8.38 g (30.0 millimole,Yield: 75 %) and the unreacted methyl 11-cyanoundecanate was 1.44 g (6.4millimole).

EXAMPLE 7

9.15 g (80.0 millimole) of ethyl 11-cyanoundecanate, 3.44 g (40.0millimole) of γ-butyrolactone and 18.15 g (40.0 millimole) of 15 wt.% ofsodium ethylate - ethanol solution were charged into a frask and heatedunder stirring. When the evaporation of ethanol from the reaction systemstarted, the degree of reduced pressure of the reaction system wascontrolled to 600 to 650 Torr and the evaporation of ethanol wascontinued until the internal temperature became 105° to 110 ° C. over 4hours. After completion of the reaction, the system was cooled and madeacidic by use of 43 ml of 1N-HCl, followed by extraction once from 100ml of methylene chloride and two times from 20 ml of methylene chloride.The product in the methylene chloride solution,α-(11-cyanoundecanoly)-γ-butyrolactone and the unreacted ethyl11-cyanoundecanate were quantified with use of a gas chromatographyaccording to the internal standard method. As a result, the producedα-(11-cyanoundecanoly)-γ-butyrolactone was 8.83 g (31.6 millimole,Yield: 79%) and the unreacted ethyl 11-cyanoundecanate was 10.77 g (45.0millimole).

REFERENCE EXAMPLE 1 (Example of production of15-hydroxy-12-ketopentadecanoic acid)

279 g (1.00 millimole) of α-(11-cyanoundecanoyl)-γ-butyrolactone, 0.68 g(10.3 millimole) of 85% potassium hydroxide and 5.66 g of water werecharged and heated under reflux over 10 hours. After completion of thereaction, the system was cooled and made acidic by use of 5 ml of4N-HCl, followed by extraction once from 70 ml of methylene chloride andtwo times from 20 ml of the same. After the methylene chloride solutionwas dried over sodium sulfate, concentration was conducted to dryness toobtain white solid. The obtained white solid was purified with use of asilicagel column by using n-hexane/ethyl acetate (1:1, volume ratio) asa developer to obtain 0.254 g (0.933 millimole, yield: 93 %) of a whitesolid.

The results of analysis of the white solid are shown below.

(1) m.p. 74° to 76 ° C.

(2) elemental analysis (in terms of C₁₅ H₂₈ O₄).

    ______________________________________                                                         C    H                                                       ______________________________________                                        Calculated (%)     66.14  10.36                                               Found (%)          66.16  10.47                                               ______________________________________                                    

(3) IR (KBr,cm⁻¹), 3250, 2920, 2850, 1700.

(4) MS (m/e, CI), 255 (M⁺ -17).

(5) 1H-NMR (CDCl₃, δ(ppm)). 1.18˜1.38 (12H, broad), 1.56˜1.65 (4H, m),1.78˜1.89 (2H, broad), 2.33˜2.36 (4H, m), 2.44˜2.57 (2H, broad),3.60˜3.70 (2H, broad).

From the above respective analysis results, it was confirmed that theproduct was 15-hydroxy-12-ketopentadecanoic acid.

Reference example 2 (Example of production of 15-hydroxy-pentadecanoicacid)

1.00 g (3.68 millimole) of 15-hydroxy-12-ketopentadecanoic acid, 0.73 g(11.0 millimole) of 85 wt.% potassium hydroxide, 0.50 g (8.5 millimole)of 85 % hydrated hydrazine and 5 ml of diethylene glycol were chargedinto a frask and heated under reflux over 1.5 hours. Subsequently, whileevaporating the produced light boiling components such as water to theoutside of the system, the internal temperature was elevated to 195° to205 ° C., and the heating under reflux was continued at the sametemperature range over 2 hours. After completion of the reaction, thesolution was cooled, diluted by addition of 5 ml of water and added with3 ml of 6N-HCl, followed by collection of the precipitated pail brownsolid by filtration. The solid was recrystallized from benzene to obtain0.81 g (3.14 millimole, Yield: 85 %) of a white crystal.

The results of analysis of the white solid are shown below.

(1) m.p. 83° to 85 ° C.

(2) elemental analysis (in terms of C₁₅ H₃₀ O₃).

    ______________________________________                                                         C    H                                                       ______________________________________                                        Calculated (%)     69.72  11.70                                               Found (%)          69.57  11.90                                               ______________________________________                                    

(3),(4) and (5).

The analysis values of IR, MS and ¹ H-NMR were the same as those of astandard product.

From the above respective analysis values, it was confirmed that theproduct was 15-hydroxypentadecanoic acid.

We claim:
 1. A method for producing α-(ω-cyanoalkanoyl)-γ-butyrolactonerepresented by the formula: ##STR4## wherein n represents an integer of7 to 11, which comprises reacting ω-cyano fatty acid ester representedby the formula:

    NC--(CH.sub.2).sub.n --COOR                                (II)

wherein R represents an alkyl group having 1 to 4 carbon atoms and n hasthe same meaning as in the above, with γ-butyrolactone in the presenceof alkali metal alcoholate represented by the formula:

    R'OM                                                       (III)

wherein R' represents an alkyl group having 1 to 4 carbon atoms and Mrepresents an alkali metal.
 2. The method according to claim 1, whereinthe ω-cyano fatty acid ester is at least one selected from the groupconsisting of methyl 8-cyanooctanate, ethyl 8-cyanooctanate, propyl8-cyanooctanate, butyl 8-cyanooctanate, methyl 9-cyanononanate, ethyl9-cyanononanate, propyl 9-cyanononanate, butyl 9-cyanononanate, methyl10-cyanodecanate, ethyl 10-cyanodecanate, propyl 10-cyanodecanate, butyl10-cyanodecanate, methyl 11-cyanoundecanate, ethyl 11-cyanoundecanate,propyl 11-cyanoundecanate, butyl 11-cyanoundecanate, methyl12-cyandodecanate, ethyl 12-cyanododecanate, propyl 12-cyanododecanateand butyl 12-cyanododecanate.
 3. The method according to claim 1,wherein the ω-cyano fatty acid ester is used in the range of 0.3 to 10mole per mole of γ-butyrolactone.
 4. The method according to claim 1,wherein the ω-cyano fatty acid ester is used in the range of 0.5 to 5mole per mole of γ-butyrolactone.
 5. The method according to claim 1,wherein the alkali metal alcoholate is selected from the groupconsisting of sodium methylate, sodium ethylate, sodium propylate,sodium butylate, potassium methylate, potassium ethylate, potassiumpropylate and potassium butylate.
 6. The method according to claim 1,wherein the alkali metal alcoholate is used under the state of analcohol solution corresponding to the alcoholate.
 7. The methodaccording to claim 1, wherein the alkali metal alcoholate is used in therange of 0.5 to 2 mole per mole of γ-butyrolactone
 8. The methodaccording to claim 1, wherein the alkali metal alcoholate is used in therange of 0.7 to 1.5 mole per mole of γ-butyrolactone.
 9. The methodaccording to claim 1, wherein the reaction is carried out in thepresence of at least one reaction solvent selected from the groupconsisting of n-hexane, n-heptane, benzene, toluene, xylene, dioxane,dimethoxyethane, diethoxyethane and diglaim.
 10. The method according toclaim 1, wherein the reaction is carried out in the temperature range of50° to 150 ° C.
 11. The method according to claim 1, wherein thereaction is carried out in the temperature range of 80° to 120 ° C. 12.The method according to claim 1, wherein the reaction is carried outunder an atmospheric pressure or a reduced pressure.
 13. The methodaccording to claim 2, whereinthe ω-cyano fatty acid ester is used in therange of 0.3 to 10 mole per mole of γ-butyrolactone; the alkali metalalcoholate is selected from the group consisting of sodium methylate,sodium ethylate, sodium propylate, sodium butylate, potassium methylate,potassium ethylate, potassium propylate and potassium butylate; thealkali metal alcoholate is used in the range of 0.5 to 2 mole per moleof γ-butyrolactone; the reaction is carried out in the presence of atleast one reaction solvent selected from the group consisting ofn-hexane, n-heptane, benzene, toluene, xylene, dioxane, dimethoxyethane,diethoxyethane and diglaim; and the reaction is carried out in thetemperature range of 50° to 150° C.
 14. The method according to claim13, whereinthe ω-cyano fatty acid ester is used in the range of 0.5 to 5mole per mole of γ-butyrolactone; the alkali metal alcoholate is used inthe range of 0.7 to 1.5 mole per mole of γ-butyrolactone; the reactionis carried out in the temperature range of 80° to 120° C.; and thereaction is carried out under an atmospheric pressure or a reducedpressure.
 15. The method according to claim 14 wherein saidγ-butyrolactone is α-(8-cyanooctanoyl)-γ-butyrolactone.
 16. The methodaccording to claim 14 wherein said γ-butyrolactone isα-(9-cyanononanoyl)-γ-butyrolactone.
 17. The method according to claim14 wherein said γ-butyrolactone is α-(10-cyanodecanoyl)-γ-butyrolactone.18. The method according to claim 14 wherein said γ-butyrolactone isα-(11-cyanoundecanoyl)-γ-butyrolactone.
 19. The method according toclaim 14 wherein said γ-butyrolactone isα-(12-dodecanoyl)-γ-butyrolactone.